Name: Alexander Flannery, PharmD, FCCM, BCCCP, BCPS

Institution: University of Kentucky

Grant: 2020 Pre-Doctoral Fellowship Award

Project Title: Alternative Renin Angiotensin Aldosterone System (RAAS) Activation and RAAS Therapeutics in Septic-Shock Associated Acute Kidney Injury

Help KidneyCure build the future , one researcher at a time.

How would you sum up your research in one sentence?

• My research aims to identify the molecular underpinnings of renin-angiotensin-aldosterone system (RAAS) dysfunction and their contribution to the pathophysiology of sepsis-associated acute kidney injury (SA-AKI) in order to develop novel therapeutics.

Provide a brief overview of the research you will conduct with help from the grant.

• From a patient population with septic shock and SA-AKI, we will investigate effector molecules of the traditional and alternative RAAS (angiotensin 1-7 and angiotensin II) and their relationship to biomarkers of kidney injury and function. We will also evaluate plasma renin and cystatin C response in patients that receive angiotensin II as part of the study. This will provide insight on the time course of RAAS disturbances in septic shock and SA-AKI as well as kidney response to angiotensin II in this setting.

What impact do you hope your research will have on patients?

• Even though sepsis is the most commonly identified risk factor for AKI, therapies remain limited to supportive care and renal replacement therapy. I hope my research undercovers a greater knowledge about traditional and alternative RAAS disturbances in SA-AKI that we can then use to design effective therapeutic approaches. This may also represent an opportunity to provide a personalized medicine approach to patients with SA-AKI.

What are your career goals at the end of the grant period? Five years out? Ten years out?

• I hope to continue developing my independence as a clinical and translational scientist and building collaborations with others across the translational spectrum working to find treatments for SA-AKI.

What inspired you to focus your research in this area?

• My clinical practice site is the medical intensive care unit, which cares primarily for patients with sepsis and septic shock. Most of the time these patients will have significant acute kidney injury associated with their sepsis. I have always dealt with this challenge from the standpoint of patient care and drug dosing, but became drawn to the underlying pathophysiology which is not as well-defined as we’d like given the scope of the problem.

What are the major challenges to beginning a career in kidney research today?

• From my perspective, major challenges include funding, the heterogeneity of kidney disease as a primary or secondary manifestation of more systemic disease, and the difficulty in translation between clinical and pre-clinical models (particularly in AKI research).

What advice would you give to others to encourage them to apply for this grant funding?

• Compared to other avenues that you could seek grant funding from, the application process was very straight forward. Even if the specific grant is not funded, it is a great opportunity to receive targeted feedback from mentors and external reviewers to consider as you reflect not only on the actual science, but also on how you are communicating your science.

Something you may not know about me is…

• I love country music and not ashamed of it.

In my free time I like to…

• Spend time with my wife and two children (ages 5 and 2).